Cinnamic acid, derivatives

2 Cinnamic Acid Derivatives D 22.2.1 Cinnamic Acids Chemistry 

Cinnamic acids are phenylpropenic acids. The phenyl ring may be substituted by hydroxy and methoxy groups. The double bond of the side chain may have cis- or trans-configuration. c s- and trans-cinnamic acids are easily interconvertible. 

Cinnamic acids are formed in higher plants and some microorganisms, e.g., several fungi and Streptomyces verticillatus as well as in animals. p-Coumaric acid, caffeic acid, ferulic acid and sinapic acid are widespread in plants. 

In plants and microorganisms cinnamic acid is formed from L-phenylalanine by phenylalanine ammonia-lyase (PAL). This enzyme catalyzes the antiperiplanar elimination of the pro 3S-hydrogen atom and of the NHg-group to yield trans-cinnamic acid (Fig. 294). Most PAL preparations deaminate also L-tyrosine, but to a smaller extend. In some organisms a special tyrosine ammonia-lyase exists. 

Sinapic acid 5-HydroxyferuIic Ferulic acid 3.4-Dimethoxy- 

Chart 33. Cinnamic acid derivatives found in the Hepaticae 

The first industrially interesting production of a chiral pharmaceutical with a chiral metal complex catalyst is the asymmetric hydrogenation of cinnamic acid derivatives to give L-DOPA, see Fig. 6.21. 

6 — HOMOGENEOUS CATALYSIS WITH TRANSITION METAL COMPLEXES 

In the first step the prochiral alkene entity coordinates to the cationic chiral rhodium centre with either one of the two enantiotopic faces (due to the asymmetry in the diphosphine ligand) which leads to the formation of two possible structures. Only one diastereoisomer of the intermediate alkene adduct is shown on Fig. 6.22 the second diastereoisomer can be easily imagined by taking the 

Having learned this, Dupont workers [52] have added a temporary auxiliary donor atom to an unsaturated substrate in order to be able to steer adduct formation, and so the enantioselectivity of the hydrogenation. For example, asymmetric hydrogenation of imines or ketones was a reaction that yielded rather low enantiomeric excesses. However, by converting these first into acyl hydrazones the hydrazide oxygen can function as the secondary complexation function and now extremely high enantiomeric excesses can be obtained (Fig. 6.23). 

Detailed studies of the hydrogenation of cinnamic acid derivatives (Fig. 6.22) by Halpern [53] and Brown [54] have revealed that the most stable intermediate of the two alkene adducts is not the one that leads to the major observed enantiomeric product, see Fig. 6.24. This means that the least stable intermediate alkene-rhodium complex reacts faster in the subsequent reaction step involving 

The oxidative addition of H2 is irreversible, and provided that no dissociation of the alkene occurs, this step determines the enantioselectivity. In general, one should realise, that the steps determining rate and selectivity need not be one and the same step of a reaction. Migration of the hydride locks the configuration of the enantiomeric centre in general, this step may 

In the examples studied, neither the dihydride intermediates nor the alkyl intermediates have been observed and therefore it seems reasonable to assume that addition of H2 is also the rate-determining step. Since the latter is a bimolecular reaction and the other ones are monomolecular rearrangement reactions one cannot say in absolute terms that oxidative addition is rate-determining.  

the intermediate alkene adduct observed in the NMR spectra is not the one leading to the major catalytic pathway, 

enantioselectivity is determined in the first irreversible step after the enantio centre was formed which is not always the same as the rate-determining step. 

The difference between this catalytic system and Wilkinson s catalyst lies in the sequence of the oxidative addition and the alkene complexation. As mentioned above, for the cationic catalysts the intermediate alkene (enamide) complex has been spectroscopically observed. Subsequently oxidative addition of H2 and insertion of the alkene occurs, followed by reductive elimination of the hydrogenation product. 

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The greater intensity of the band of the metabolite at 220 mis probably due to the presence of a second, superimposed chromophore which could also account for the shift of the minimum. On the other hand, the band near 300 m/u. has the expected intensity. Its broadness and displacement towards longer wavelength are probably due to the presence of a substituent on the double bond or benzenoid ring. That the assignment to a coumaroyl chromophore is essentially correct is evidenced by the fact that both M and the model compound underwent the same type of reaction on irradiation in the near-ultraviolet (Figure 4). The observed isosbestic points imply that the photoreaction is a simple one, such as A -> B or A = B, and is obviously the well-known light-induced trans- to c/r-isomerization (7) of cinnamic acid derivatives. 

Chlorosulfo-de-diazoniation 241 CIDNP, see Dediazoniations Cinnamic acid derivatives, reaction with ArNj 243 Cinnolines 140 f. 

In recent years, the catalytic asymmetric hydrogenation of a-acylamino acrylic or cinnamic acid derivatives has been widely investigated as a method for preparing chiral a-amino acids, and considerable efforts have been devoted for developing new chiral ligands and complexes to this end. In this context, simple chiral phosphinous amides as well as chiral bis(aminophosphanes) have found notorious applications as ligands in Rh(I) complexes, which have been used in the asymmetric hydrogenation of a-acylamino acrylic acid derivatives (Scheme 43). 

Three distinct chemotypes were observed. Taxa from each of the three areas noted above exhibited unique combinations of the compounds and compound types, although there was a degree of variation within most groups, as one might expect. The North American chemotype was characterized by very high frequency of the sulfated cinnamic-acid derivatives, a frequency of flavonol derivatives of... 

The chemical formulae for a variety of plant phenols are given in Fig. 16.2, including examples of simpler phenols, such as cinnamic acid derivative, and of tocopherols, flavonoids, flavonoid glycosides and anthocyanidins. The flavonoids include the following subclasses flavanones (taxifolin), flavones (luteolin), flavonols (quercetin) and flavanols (catechin/epicatechin). The... 

Wine and by-products Cinnamic acid derivatives, anthocyanins and flavanols dominate (10 to 20 J,M gallic acid equivalents) Oil-in-water emulsion (dressing model) Red wine yields better protection, but phenols in white and rose wine seem more efficient on a molar basis Sanchez-Moreno et al., 2000... 

Recent scientific investigations of natural polyphenols have demonstrated their powerful antioxidant property (Niki et al, 1995). Several classes of polyphenols have been chemically identified. Some of these are grape polyphenols, tea polyphenols, soy polyphenols, oligomeric proanthocyanidines (OPA) and other natural polyphenols of the flavone class. Rice bran polyphenols are different from the above in that they are p-hydroxy cinnamic acid derivatives such as p-coumaric acid, ferulic acid and p-sinapic acid. Tricin, a flavone derivative, has also been isolated from rice bran. 

A number of carboxylic acids are found in nature and also present in metabolic pathways. Accordingly, if monobasic acids are smoothly decarboxylated, they are expected to provide us with new routes to supply useful materials for chemical industry without depending on petroleum. Actually, there are some already known examples. The representative examples are the decarboxylation of cinnamic acid derivatives (Table 8). ... 

Although the reaction mechanism of this type of reactions is not fully elucidated, it is easily anticipated that no intramolecular special stabilization effect for the carbanion generated from decarboxylation is expected, different from the case of malonic acid-type compounds. Moreover, cinnamic acid derivatives that have both the electron-donating and withdrawing substituents have been reported to undergo this reaction. This fact suggests that the enzyme itself stabilizes the transition state without the aid of mesomeric and inductive effects of the other part of the substrate molecule itself. If such unknown mechanism also works for other... 

K. Haider and J. P. Martin, Decomposition of specifically carbon-14 labeled benzoic and cinnamic acid derivatives in soil. Soil Sci. Soc. Am. Proc. 39 651 (1975). 

Arcmatic compounds phenols, phenolic acids, cinnamic acid derivatives, coumarins, flavonoids, quinones, and tannins, all of which are aromatic compounds, comprise the largest group of secondary plant products. They are often referred to as "phenolics" and have been identified as allelopathic agents in more instances than all of the other classes of compounds combined 5). 

Several additional benzoic and cinnamic acid derivatives were tested (28-31). 

Two hypotheses have been proposed to explain how phenolic acids directly increase membrane permeability. The first is that the compounds solubilize into cellular membranes, and thus cause a "loosening" of the membrane structure so that minerals can leak across the membrane (28-30, 42). Support for this hypothesis comes from the fact that the extent of inhibition of electrical potentials correlates with the log P (partition coefficient of a compound between octanol and water) for various benzoic and cinnamic acid derivatives (Figure 5). 

Recently, we developed a new matrix based on nanoparticle technologies, which have a completely different chemical structure from benzoic or cinnamic acid derivatives.17 Derivatives of these matrices may enhance specific molecules in IMS. 

The mechanism of the formation of compound 67 has been studied by Higa and Krubsack [41] in detail, as shown in Scheme 15. Namely, the initial step of the reaction of the cinnamic acid derivative 66 with thionyl chloride is an electrophilic addition of thionyl chloride across the double bond of cin-namoyl chloride to form the sulfinyl chloride intermediate (66a), which is then converted to 68 by the Pummerer reaction. Dehydrochlorination of 68... 

The use of 2 equiv. of MonoPhos (10 a) in the rhodium-catalyzed enantioselective hydrogenation of the key cinnamic acid derivative 15 resulted in the formation of 16 in 50% conversion and 20% ee after 5 h in isopropanol at 60 °C and 25 bar of hydrogen. Other phosphoramidites, such as the sterically demanding ligand 10 c, resulted in slightly better activity and enantioselectivity. In seeking a... 

R. C. Beavis and B. T. Chait. Cinnamic Acid Derivatives as Matrices for Ultraviolet Laser Desorption Mass Spectrometry of Proteins. Rapid Commun. Mass Spectrom., 3(1989) 432-435. 

The asymmetric hydrogenation of cinnamic acid derivatives has been developed by Knowles at Monsanto [4], The synthesis of L-dopa (Figure 4.3), a drug for the treatment of Parkinson s disease, has been developed and is applied on an industrial scale. Knowles received the Nobel Prize for Chemistry in 2001 together with Noyori (see below, BINAP ) and Sharpless (asymmetric epoxidation). 

The first modern day negative photoresists were developed by the Eastman Kodak Company which utilized cyclized rubbers and cinnamic acid derivatives as photosensitive crosslinking agents (42). The first commercially important photoresist based on this chemistry was known as KPR, which was of a cinnamate ester of polyvinyl alcohol. It was introduced by Kodak in 1954. 

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